Killer cell immunoglobulin-like two-domain short-tail receptor 2 (KIR2DS2) is an activating KIR receptor invariably expressed on the cell surface of NK cells and subsets of T cells. The ligand specificity of KIR2DS2 is unknown; it does not bind the HLA-Cw3 molecules recognised by the inhibitory receptor KIR2DL2, despite 99% extracellular amino acid identity (Saulquin et al. 2003). In the presence of DAP12, cross-linking of KIR2DS2 with monoclonal antibody leads to phosphorylation of JNK and ERK and activation of both cytotoxicity and IFN-production.